title: Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain.
abstract: OBJECTIVE
  Fibroblasts can be directly reprogrammed to cardiomyocyte-like cells by introducing defined genes. However, the reprogramming efficiency remains low, delaying the clinical application of this strategy to regenerative cardiology. We previously showed that fusion of the MyoD transactivation domain to the pluripotency transcription factor Oct4 facilitated the transcriptional activity of Oct4, resulting in highly efficient production of induced pluripotent stem cells. We examined whether the same approach can be applied to cardiac transcription factors to facilitate cardiac reprogramming.
  
  
  RESULTS
  We fused the MyoD domain to Mef2c, Gata4, Hand2, and Tbx5 and transduced these genes in various combinations into mouse non-cardiac fibroblasts. Transduction of the chimeric Mef2c with the wild-types of the other three genes produced much larger beating clusters of cardiomyocyte-like cells faster than the combination of the four wild-type genes, with an efficiency of 3.5%, >15-fold greater than the wild-type genes.
  
  
  CONCLUSIONS
  Fusion of a powerful transactivation domain to heterologous factors can increase the efficiency of direct reprogramming of fibroblasts to cardiomyocytes.
authors.affiliation: Stem Cell Institute, MTRF Room 2-216, University of Minnesota, 2001 6th St SE, Minneapolis, MN 55455, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirai
authors.forename: Nobuko
authors.initials: N
authors.lastname: Katoku-Kikyo
authors.forename: Susan A
authors.initials: SA
authors.lastname: Keirstead
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kikyo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005347:Fibroblasts / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D057026:Induced Pluripotent Stem Cells; D064326:MEF2 Transcription Factors / Q000502:physiology; D051379:Mice; D017570:MyoD Protein / Q000737:chemistry / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000502:physiology; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse
keywords: Cardiomyocytes; Direct reprogramming; Transcription factors